The overall objective of this research is to elucidate the molecular, biochemical and cellular events responsible for determining susceptibility or resistance of the snail, Biomphalaria glabrata, to infection with the human blood fluke, Schistosoma mansoni. The system used consists of the NIH-Sm-PR-1 strain of S. mansoni, to which PR albino, M-line B. glabrata are susceptible, and the pigmented 10-R2 and the albino 13-16-R1 strains which are actively resistant to the parasite. There are three major goals of this proposal: 1. During the past grant period a 55 kDa polypeptide in the serum of 10-R2 B. glabrata that binds to S. mansoni sporocysts was discovered. Interestingly, similar molecular weight proteins from M-line serum did not bind to the parasite. Therefore, the structure and function of serum polypeptides (from the three snail strains) will be characterized using electrophoretic and peptide mapping techniques. Antibodies to these polypeptides will be generated, and immunofluorescent antibody tests (IFAT) and immunoscanning electron microscopy (ISEM) will be used to assess their binding properties. Lastly, these reagents will be used in important functional analysis experiments using several in vitro and in vivo systems. 2. During the past grant period an 80 kDa surface-polypeptide unique to hemocytes from resistant B. glabrata was identified. Such a polypeptide may play a crucial role in mediating larval schistosome destruction. Therefore, hemocytes will be thoroughly characterized by surface-labeling, electrophoretic and peptide mapping techniques. Next, antibodies to the major surface proteins will be generated, and IFAT and ISEM will be used to determine their binding characteristics. Furthermore, these reagents will be used in a variety of important functional analysis experiments. 3. Since the mechanism by which hemocytes respond to schistosome infection is unknown, hemocyte formation in B. glabrata will be studied by following the fate of injected thymidine-14C. Hemocyte activation will be examined by measuring RNA and protein synthesis using radioactive precursors. Finally, surface characteristics of activated hemocytes, and the functional relevance of these cells will be evaluated using several in vitro systems. This research will make a significant contribution to the understanding of how vector competence is manifested in schistosome-snail interactions, which will be useful in designing rational vector control programs.